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Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

2020; Cell Press; Volume: 52; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2020.01.002

1097-4180

Aoife McGinley, Caroline E. Sutton, Sarah C. Edwards, Charlotte M. Leane, Joseph DeCourcey, Ana Teijeiro, John A. Hamilton, Louis Boon, Nabil Djouder, Kingston H. G. Mills,

Dermatology and Skin Diseases

Interleukin-17A (IL-17A) is a major mediator of tissue inflammation in many autoimmune diseases. Anti-IL-17A is an effective treatment for psoriasis and is showing promise in clinical trials in multiple sclerosis. In this study, we find that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) are resistant to disease and have defective priming of IL-17-secreting γδ T (γδT17) cells and Th17 cells. However, T cells from Il17a−/− mice induce EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. Furthermore, treatment with IL-1β or IL-17A at induction of EAE restores disease in Il17a−/− mice. Importantly, mobilization of IL-1β-producing neutrophils and inflammatory monocytes and activation of γδT17 cells is reduced in Il17a−/− mice. Our findings demonstrate that a key function of IL-17A in central nervous system (CNS) autoimmunity is to recruit IL-1β-secreting myeloid cells that prime pathogenic γδT17 and Th17 cells.